The nanomaterial landscape is so vast that a combinatorial approach is required to understand the underlying structure-function relationships, which presents a challenge for chemical synthesis. High throughput screening is an invaluable tool for scientific discovery in many fields. A key technology that enables these high throughput approaches is the ability to synthesize combinatorial libraries of compounds and reaction conditions that allow for the study of a variety of samples in unison. As such, combinatorial libraries have been utilized in diverse fields including catalysis, drug discovery, and basic cell biology. At current, such massively parallel experiments are typically performed using advanced liquid handling systems that deposit nanoliter scale fluid volumes into plates with as many as 1536 distinct wells. However, the path to utilizing smaller volumes and higher throughput faces major challenges as techniques for depositing controlled quantities of chemically specific materials in a high throughput manner are very limited. Ink jet printing, both through electrohydrodynamic jetting and ultrasonic focusing, can in some cases generate sub femptoliter-scale volumes, but is limited in throughput by serial printing afforded by a single nozzle and low registration accuracy owing to the dewetting process. Similarly, the direct write of materials from a physical scanning probe, or dip-pen nanolithography, can reliably pattern sub-attoliter volumes, but throughput is a critical limitation.
Recently, it has been recognized that by using a massive array of polymeric probes on a rigid backing layer is a path to overcoming the challenge by providing as many as 11 million probes that can operate in synchrony, the challenge from the perspective of using these for constructing combinatorial libraries is generating unique chemical features with each pen in the array. A major avenue of research has been to exploit the unique cantilever-free architecture in ways that transform the lithographic capabilities. For instance, due to the large coefficient of thermal expansion inherent to elastomers, local heating can be used to independently address specific probes. Furthermore, due the amount of material deposited is related to the tip-sample pressure due to the compliant nature of the pens. This fact has been exploited by deliberately tilting the pen array with respect to a surface, it is possible to pattern a centimeter-scale array of features wherein the feature size varies continuously across the array.
Chemical heterogeneity has proven more difficult to systematically introduce as currently the only methods that have been explored has been by inking tips in blocks using micro-contact printing or individually inking them using ink jet printing. While these present an advantage in terms of scaling, one ink jet printing operation is needed to ink a single pen with ˜50 micron pitch which will subsequently be used to pattern thousands of features with submicron pitch, it is still not practical for scaling to millions of pens. Indeed, for many types of experiments, independent control over every pen in the array is unnecessary because what is needed is a continuously varying gradient in composition. From this perspective, advances in how to rapidly ink polymer pen arrays with non-uniform ink composition would bear important implications for the synthesis of combinatorial arrays for rapid materials discovery.